A single-arm, phase II, multicenter trial of sunitinib maleate (SU) in locally advanced or metastatic pheochromocytoma/paraganglioma (PC/PG): Interim results.

Abstract

431 Background: Metastatic PC/PG is rare and may be sporadic or have a genetic basis. Treatment remains challenging in the absence of well-controlled randomized trials. Case reports suggest clinical activity of SU in this setting. We aim to prospectively evaluate radiological and biochemical response to SU, and assess its toxicity profile in PC/PG. Methods: This is an ongoing single-arm, phase II, multicenter, investigator-initiated clinical trial, enrolling patients (pts) with metastatic or unresectable locally advanced malignant PG or PC with ECOG PS 0-2, no previous treatment with tyrosine kinase inhibitors, and evidence of radiological progression or disease-related symptoms. All pts receive 50mg SU daily at standard dosing, following blood pressure stabilization, and are assessed for radiological and biochemical response (with urine metanephrines, catecholamines or serum chromogranin A) q12 weeks until disease progression, unacceptable toxicity or pts withdrawal. Futility was defined as no documented responses within the first 14 patients and would have led to trial cessation. Results: Since May 2009, 14 pts enrolled in 3 academic hospitals (Canada and the Netherlands). Interim results of 10 pts are presented (pts characteristics are tabulated). Two pts had symptoms related to hormonal-excess and both had clinical improvement on SU. All 10 pts had biochemical evidence of hormonal excess, of which 5 had biochemical response (50%). Best radiological responses achieved were partial response (3/10 pts; 30%, 1 unconfirmed), stable disease > 3 months (6/10; 60%) and progressive disease (1/10; 10%). Adverse events were consistent with known side-effects of SU. Seven pts had toxicity-related dose reductions, contributing to treatment cessation in two. Conclusions: This trial surpassed the pre-specified futility stopping rule with the current documented responses on SU and with durable patient benefit seen. Updated data will be presented and discussed. Clinical trial information: NCT00843037. [Table: see text]